Abstract

Background

More than 200 studies related to nucleic acid amplification (NAA) tests to detect
Mycobacterium tuberculosis directly from clinical specimens have appeared in the world literature since this
technology was first introduced. NAA tests come as either commercial kits or as tests
designed by the reporting investigators themselves (in-house tests). In-house tests
vary widely in their accuracy, and factors that contribute to heterogeneity in test
accuracy are not well characterized. Here, we used meta-analytical methods, including
meta-regression, to identify factors related to study design and assay protocols that
affect test accuracy in order to identify those factors associated with high estimates
of accuracy.

Results

By searching multiple databases and sources, we identified 2520 potentially relevant
citations, and analyzed 84 separate studies from 65 publications that dealt with in-house
NAA tests to detect M. tuberculosis in sputum samples. Sources of heterogeneity in test accuracy estimates were determined
by subgroup and meta-regression analyses. Among 84 studies analyzed, the sensitivity
and specificity estimates varied widely; sensitivity varied from 9.4% to 100%, and
specificity estimates ranged from 5.6% to 100%. In the meta-regression analysis, the
use of IS6110 as a target, and the use of nested PCR methods appeared to be significantly associated
with higher diagnostic accuracy.

Conclusion

Estimates of accuracy of in-house NAA tests for tuberculosis are highly heterogeneous.
The use of IS6110 as an amplification target, and the use of nested PCR methods appeared to be associated
with higher diagnostic accuracy. However, the substantial heterogeneity in both sensitivity
and specificity of the in-house NAA tests rendered clinically useful estimates of
test accuracy difficult. Future development of NAA-based tests to detect M. tuberculosis from sputum specimens should take into consideration these findings in improving accuracy
of in-house NAA tests.